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Volume 12
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10.3390/cells12060910
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Article

The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor

by
Nourhan Hassan
1,2,
Nico Bückreiß
3,
Janes Efing
1,
Marie Schulz-Fincke
3,
Philipp König
3,
Burkhard Greve
4,
Gerd Bendas
3,† and
Martin Götte
1,*,†
1
Department of Gynecology and Obstetrics, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
2
Biotechnology/Biomolecular Chemistry Program, Faculty of Science, Cairo University, Giza 12613, Egypt
3
Pharmaceutical Department, University Bonn, An der Immenburg 4, 53225 Bonn, Germany
4
Department of Radiotherapy-Radiooncology, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
†
Both authors are joint senior authors of this work.
Cells 2023, 12(6), 910; https://doi.org/10.3390/cells12060910
Submission received: 30 January 2023 / Revised: 8 March 2023 / Accepted: 14 March 2023 / Published: 16 March 2023
(This article belongs to the Special Issue Extracellular Matrix-mediated Cancer Cells)
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Abstract

Syndecan-1 (Sdc-1) upregulation is associated with poor prognosis in breast cancer. Sdc-1 knockdown results in reduced angiogenesis and the dysregulation of tissue factor (TF) pathway constituents. Here, we evaluate the regulatory mechanisms and functional consequences of the Sdc-1/TF-axis using Sdc-1 knockdown and overexpression approaches in MCF-7 and MDA-MB-231 breast cancer cells. Gene expression was analyzed by means of qPCR. Thrombin generation and cell migration were detected. Cell-cycle progression and apoptosis were investigated using flow cytometry. In MDA-MB-231 cells, IL6, IL8, VEGF, and IGFR-dependent signaling affected TF pathway expression depending on Sdc-1. Notably, Sdc-1 depletion and TF pathway inhibitor (TFPI) synergistically affected PTEN, MAPK, and STAT3 signaling. At the functional level, the antiproliferative and pro-apoptotic effects of TFPI depended on Sdc-1, whereas Sdc-1’s modulation of cell motility was not affected by TFPI. Sdc-1 overexpression in MCF-7 and MDA-MB-231 cells led to increased TF expression, inducing a procoagulative phenotype, as indicated by the activation of human platelets and increased thrombin formation. A novel understanding of the functional interplay between Sdc-1 and the TF pathway may be compatible with the classical co-receptor role of Sdc-1 in cytokine signaling. This opens up the possibility of a new functional understanding, with Sdc-1 fostering coagulation and platelet communication as the key to the hematogenous metastatic spread of breast cancer cells.
Keywords: apoptosis; breast cancer; cell cycle; cell motility; heparan sulfate; platelets; signal transduction; syndecan-1; thrombin; tissue factor apoptosis; breast cancer; cell cycle; cell motility; heparan sulfate; platelets; signal transduction; syndecan-1; thrombin; tissue factor
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MDPI and ACS Style

Hassan, N.; Bückreiß, N.; Efing, J.; Schulz-Fincke, M.; König, P.; Greve, B.; Bendas, G.; Götte, M. The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor. Cells 2023, 12, 910. https://doi.org/10.3390/cells12060910

AMA Style

Hassan N, Bückreiß N, Efing J, Schulz-Fincke M, König P, Greve B, Bendas G, Götte M. The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor. Cells. 2023; 12(6):910. https://doi.org/10.3390/cells12060910

Chicago/Turabian Style

Hassan, Nourhan, Nico Bückreiß, Janes Efing, Marie Schulz-Fincke, Philipp König, Burkhard Greve, Gerd Bendas, and Martin Götte. 2023. "The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor" Cells 12, no. 6: 910. https://doi.org/10.3390/cells12060910

APA Style

Hassan, N., Bückreiß, N., Efing, J., Schulz-Fincke, M., König, P., Greve, B., Bendas, G., & Götte, M. (2023). The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor. Cells, 12(6), 910. https://doi.org/10.3390/cells12060910

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